Project 4: Post-Exposure Biomarkers and Remediation of Radionuclide Contaminants

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PROJECT 4: ABSTRACT In the last several years, a sense of urgency and a renewed interest in the study of radionuclide chemistry and biology have emerged, as threats of nuclear terrorism have become more plausible, as investigational medical tools have sought the radioactive properties of radionuclides, and as the risk of environmental contamination and human exposure to radioisotopes consequently increased. In this project, we will pursue the analysis of radionuclide distribution beyond the MACRO into the MESO, MICRO and NANO scales, in order to improve dosimetry modeling and biokinetics analyses, in line with biological endpoints, thereby enabling meaningful countermeasure development in the context of internal emitter exposures. The radiation damage and health risk presented by internalized radionuclides can be mitigated by the use of mitigators, such as decorporation agents, that reduce internal contamination. However, most effective agents enhance the elimination of only a limited range of radionuclides, and some are formulated in ways that would make administration in mass casualty situations challenging. Therefore, the development of improved decorporation therapies and better delivery systems for chelators is a research priority in the area of radiological and nuclear threat countermeasures. This project specifically addresses the urgent need to develop and implement an improved therapy for radioisotope contamination of a large population. It will establish biokinetic profiles in adult and juvenile animal models, enable the discovery of biomarkers of exposure, and extend the indication of a new therapeutic decorporation agent to selected radioisotopes in the form of inhaled particulates, by demonstrating the post-exposure potency of this product at preventing long-term lung deposition and subsequent damage. In addition, by correlating different biomarkers of radiation toxicity to countermeasure’s efficacy, this research will provide the foundational data needed to determine the need for, and course and endpoint of treatment.